Cell-cell adhesion is a fundamental biological function. It underlies the structure of tissues and their dynamic reorganization during processes as important as morphogenesis, cell locomotion and signaling. In addition to the high level of complexity in the identified biochemical pathways, it has recently become clear that mechanical effects also play an important role. For example, pushing cells together or increasing their contractile forces by changing the substrate stiffness reinforces the strength of contacts. Furthermore, since homeostatic pressure arising from the balance of cell division and cell death is important in achieving the mechanical integrity of tissues it is also assumed to affect cell-cell adhesion. However, the physical origin of force-sensitive adhesion remains an open question. This is so particularly because the theoretical models used for relevant study are derived from the behavior of simplified model membranes that lack mechanical resilience.
Although these models successfully describe the kinetics and energetics of adhesion in the absence of rigidity, they cannot address the effects of force. In a cell, rigidity arises from the cytoskeleton scaffold and mechanical coupling with neighboring cells in the surrounding tissue. As a result, individual cells are viscoelastic with a bulk modulus of about 1 kPa. Moreover, the interplay between cortical tension and adhesive interactions with neighbors gives rise to a surface tension in cellular aggregates.
Biomimetic modeling that describes all aspects of cellular interaction, including the effects of force, is essential for exploring avenues of treatment of diseases characterized by abnormal cell-cell adhesion. Otherwise, entire avenues of treatment might lie unexplored. Such diseases span a vast swath of pathology, but may be exemplified by the following: human genetic diseases may be caused by inability to express a specific adhesion molecule, such as in leukocyte adhesion deficiency-I (LAD-I), where patients do not express the β2-integrin subunit precursor. This integrin is required for leukocytes to adhere to the blood vessel wall during inflammation in order to fight infection. The leukocytes from LAD-I patients fail to adhere and patients exhibit serious episodes of infection that can be life threatening. Additionally, in tumor metastasis, tumors that spread through the circulatory system use mechanisms of cell adhesion to establish new tumors in the body. Still further, many viruses also have adhesion molecules required for viral binding to host cells. For example, influenza virus has a hemagglutinin on its surface that is required for recognition of the sugar sialic acid on host cell surface molecules. HIV has an adhesion molecule termed gp120 that binds to its ligand CD4, which is expressed on lymphocytes.
Therefore, there remains a need for novel approaches to treatment of these conditions, which can be provided by the development of a biomimetic system capable of replicating the effects of force on cell-cell adhesion in order to form a proper understanding of the effects of such force on cellular interactions. Such understanding will allow applications to chemical and biological systems for commercial uses.